The advent of hybridoma techniques has brought about the possibility of producing homogeneous populations of highly specific antibodies against a variety of antigens. These monoclonal antibodies have promise in the diagnosis and treatment of many diseases. Loss of antibody from the cell surface or failure of antibody alone to show therapeutic effects has posed a serious problem with regard to the potential usefulness of monoclonal antibodies (hereinafter MoAb) in clinical therapy.
Immunotoxins are hybrid molecules consisting of a MoAB covalently bound to a plant or bacterial toxin. One such toxin, ricin, is a glycoprotein consisting of an A chain, which is toxic, and a B chain. The A chain is not capable of binding or penetrating cell membranes unless bound to a B chain. Ricin B chain binds galactose receptors on the cell surface.
In order to use an immunotoxin (hereinafter IT) having ricin linked to a MoAb, lactose must be added to prevent ricin binding to galactose receptors on cells other than the targeted cells.
It has been found by the inventors that IT induce internalization of the MoAb-toxin conjugate, rather than shedding from the cell surface. In contrast, antibody alone can be shed. "Arming" MoAb by toxin and radionuclide conjugation may, therefore, solve problems currently encountered in attempts at therapy with MoAb alone. Thus, there may be an advantage in the clinical use of IT and RIT. IT's have been employed by the inventors as purgative reagents for bone marrow transplantation and may be used as therapeutic reagents for the treatment of solid tumors. In cancer therapy, it is important to selectively kill every cancerous cell which is not possible with the use of MoAbs alone. Even IT may not kill all tumor cells in larger tumors. Therefore, the additional killing effects of irradiation are desirable.